This review and commentary is the product of an invited lecture called “Autoimmunity: PANS/PANDAS” presented at the 2018 Neurobiology of Diseases in Children Symposium in Chicago, IL. The talk ...addressed clinical and scientific questions and recently published data. At this time, among highly experienced and respected clinicians and researchers spanning relevant disciplines, there is substantial controversy regarding a role for inflammation in producing tics and obsessive-compulsive disorder. This commentary summarizes these controversies, discusses reasons for opposing views on best clinical practices, and concludes with suggestions for pathways forward.
Vertebrate glycoproteins and glycolipids are synthesized in complex biosynthetic pathways localized predominantly within membrane compartments of the secretory pathway. The enzymes that catalyze ...these reactions are exquisitely specific, yet few have been extensively characterized because of challenges associated with their recombinant expression as functional products. We used a modular approach to create an expression vector library encoding all known human glycosyltransferases, glycoside hydrolases, and sulfotransferases, as well as other glycan-modifying enzymes. We then expressed the enzymes as secreted catalytic domain fusion proteins in mammalian and insect cell hosts, purified and characterized a subset of the enzymes, and determined the structure of one enzyme, the sialyltransferase ST6GalNAcII. Many enzymes were produced at high yields and at similar levels in both hosts, but individual protein expression levels varied widely. This expression vector library will be a transformative resource for recombinant enzyme production, broadly enabling structure-function studies and expanding applications of these enzymes in glycochemistry and glycobiology.
Background and purpose
In 2020, health professionals witnessed a dramatic increase in referrals of young people with rapid onset of severe tic‐like behaviours. We assembled a working group to develop ...criteria for the clinical diagnosis of functional tic‐like behaviours (FTLBs) to help neurologists, pediatricians, psychiatrists, and psychologists recognize and diagnose this condition.
Methods
We used a formal consensus development process, using a multiround, web‐based Delphi survey. The survey was based on an in‐person discussion at the European Society for the Study of Tourette Syndrome (ESSTS) meeting in Lausanne in June 2022. Members of an invited group with extensive clinical experience working with patients with Tourette syndrome and FTLBs discussed potential clinical criteria for diagnosis of FTLBs. An initial set of criteria were developed based on common clinical experiences and review of the literature on FTLBs and revised through iterative discussions, resulting in the survey items for voting.
Results
In total, 24 members of the working group were invited to participate in the Delphi process. We propose that there are three major criteria and two minor criteria to support the clinical diagnosis of FTLBs. A clinically definite diagnosis of FTLBs can be confirmed by the presence of all three major criteria. A clinically probable diagnosis of FTLBs can be confirmed by the presence of two major criteria and one minor criterion.
Conclusions
Distinguishing FTLBs from primary tics is important due to the distinct treatment paths required for these two conditions. A limitation of the ESSTS 2022 criteria is that they lack prospective testing of their sensitivity and specificity.
Pediatric neurology is the medical subspecialty responsible for diagnosing and managing diseases and disorders of the nervous system in childhood and adolescence. In many, but not all, regions of the ...world, the discipline of pediatric neurology is recognized as a specialty or subspecialty of either neurology or pediatrics. Significant knowledge and competencies in this area are necessary to be effective in clinical practice. The need for this is driven by the high burden of disease from neurologic conditions in children and the effect on their families. As the first part of a multistaged project under the auspices of the International Child Neurology Association, in collaboration with key stakeholders, a survey was undertaken to establish which countries have practicing child neurologists. For those countries that have child neurologists, the survey established the number of practitioners and which countries have access to in-country child neurology training. Responses were obtained from 177 countries. Worldwide, there is a median of 0.07 and mean of 0.39 child neurologists per 100,000 population. The greatest deficits in child neurology specialists and access to training were evident in countries which fell under the World Bank rating of low-income country status (range of 0-0.008 child neurologists per 100,000 population). Seventy-three percent of low-income countries lack access to child neurologists: The majority are in the African and South-East Asia regions. For the population of 1.37 billion in the continent of Africa, there were 324 child neurologists, equating to a median of 0.01 per 100,000 population in comparison with a median of 0.59 child neurologists per 100,000 across high-income countries. Ninety-four countries had capacity to support in-country pediatric neurology training. Worldwide, there are inadequate numbers of child neurologists and a great need for increased training capacity.
L-histidine decarboxylase and Tourette's syndrome Ercan-Sencicek, A Gulhan; Stillman, Althea A; Ghosh, Ananda K ...
Nature reviews. Neuroscience,
05/2010, Letnik:
362, Številka:
20
Journal Article
Recenzirano
Odprti dostop
Tourette's syndrome is a common developmental neuropsychiatric disorder characterized by chronic motor and vocal tics. Despite a strong genetic contribution, inheritance is complex, and risk alleles ...have proven difficult to identify. Here, we describe an analysis of linkage in a two-generation pedigree leading to the identification of a rare functional mutation in the HDC gene encoding L-histidine decarboxylase, the rate-limiting enzyme in histamine biosynthesis. Our findings, together with previously published data from model systems, point to a role for histaminergic neurotransmission in the mechanism and modulation of Tourette's syndrome and tics.
Zika virus (ZIKV) emerged on a global scale and no licensed vaccine ensures long-lasting anti-ZIKV immunity. Here we report the design and comparative evaluation of four replication-deficient ...chimpanzee adenoviral (ChAdOx1) ZIKV vaccine candidates comprising the addition or deletion of precursor membrane (prM) and envelope, with or without its transmembrane domain (TM). A single, non-adjuvanted vaccination of ChAdOx1 ZIKV vaccines elicits suitable levels of protective responses in mice challenged with ZIKV. ChAdOx1 prME ∆TM encoding prM and envelope without TM provides 100% protection, as well as long-lasting anti-envelope immune responses and no evidence of in vitro antibody-dependent enhancement to dengue virus. Deletion of prM and addition of TM reduces protective efficacy and yields lower anti-envelope responses. Our finding that immunity against ZIKV can be enhanced by modulating antigen membrane anchoring highlights important parameters in the design of viral vectored ZIKV vaccines to support further clinical assessments.
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